title: Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
abstract: A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gammadelta T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate gammadelta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gammadelta T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new potential drug candidate for cancer treatment.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, Italy. smd@unife.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Simoni
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Invidiata
authors.forename: Marco
authors.initials: M
authors.lastname: Eleopra
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rondanin
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baruchello
authors.forename: Stefano
authors.initials: S
authors.lastname: Provera
authors.forename: Carla
authors.initials: C
authors.lastname: Marchioro
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Limongelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Aaron
authors.initials: A
authors.lastname: Kwaasi
authors.forename: James
authors.initials: J
authors.lastname: Dunford
authors.forename: Simona
authors.initials: S
authors.lastname: Buccheri
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta